PAK4 and Gastric Cancer

A large‐scale association study evaluating the epidermal growth factor receptor (EGFR) pathway in a Han Chinese population has identified PAK4 (HGNC:16059) as one of the genes significantly associated with gastric cancer (MONDO_0001056). In this study, 3443 SNPs across 127 EGFR pathway genes were analyzed in 1758 gastric cancer cases and 2111 controls, demonstrating statistical significance at both pathway and gene levels (PMID:23874846). This association was observed amidst a broader genetic analysis that included multiple candidate genes and provided evidence that common genetic variation in PAK4 may contribute to cancer risk.

Genetic evidence for the PAK4 and gastric cancer association is supported by robust case–control data with a substantial number of cases. Although classical familial segregation data were not reported, the gene‐level association across a multi‐patient cohort lends moderate support to PAK4’s role in gastric tumorigenesis (PMID:23874846). The analysis did not focus on individual rare variants; rather, it assessed the contribution of common SNPs within a biologically relevant pathway.

In terms of genetic evidence details, the study utilized scores drawn from genome‑wide association study methodologies to implicate PAK4 without pinpointing any single causative variant. No specific HGVS‐formatted coding changes were reported in the gastric cancer cohort. As a consequence, while the overall association is compelling at the gene level, curated variant data for this particular gene–disease relationship remain pending, and the reported variant list remains empty for this context.

Functional studies provide additional support by demonstrating that the PAK4 protein exhibits key oncogenic properties. Experimental investigations have revealed that PAK4 kinase activity is critical for anchorage‑independent growth and enhanced cell motility – hallmarks of cancer progression (PMID:11668177). These in vitro assays, although performed in different tumor models, bolster the biological plausibility of PAK4 contributing to cancer development and may extend to the context of gastric cancer.

Integration of the genetic association and functional experimental evidence yields a coherent narrative that supports a moderate level of clinical validity for the association between PAK4 and gastric cancer. The statistical significance observed in large patient cohorts, together with functional data demonstrating that deregulation of PAK4 leads to oncogenic cellular behaviors, underscore its potential role as a susceptibility factor. While additional familial segregation and variant-specific evidence could further strengthen the association, the current evidence base supports the clinical utility of considering PAK4 in diagnostic decision‑making for gastric cancer.

Key take‑home: The convergence of substantial gene‑level association data and complementary functional studies supports a moderate yet actionable link between PAK4 and gastric cancer risk, underscoring its potential as a marker in clinical and commercial applications.

References

• PloS One • 2013 • Genetic variants in epidermal growth factor receptor pathway genes and risk of esophageal squamous cell carcinoma and gastric cancer in a Chinese population PMID:23874846
• The Journal of Biological Chemistry • 2002 • Requirement for PAK4 in the anchorage-independent growth of human cancer cell lines PMID:11668177

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